心脏瓣膜病心房颤动患者心房肌超极化激活环化核苷酸门控通道基因表达的研究

Gene expression of atrial hyperpolarization-acfivated cyclic nucleotide-gated channel in patients with atrial fibrillation associated with valvular heart disease

目的研究心脏瓣膜病心房颤动（房颤）患者心房肌超极化激活环化核苷酸门控通道（HCN）各亚型及其调控因子环腺苷酸（cAMP）的基因转录，探讨房颤患者心房肌超极化激活电流（If）改变的分子机制。方法心外科心脏瓣膜病需开胸换瓣的病人45例，分为两组，其中房颤者27例，窦性心律者18例，术中取左心房组织，采用半定量逆转录-聚合酶链反应（RT—PCR）测定HCN1、HCN2、HCN4、cAMP的mRNA的含量。结果同窦性心律组相比，房颤组患者心房肌HCN2、14CN4的mRNA表达水平上调（P〈0．05），HCN1、cAMP的mRNA表达水平在房颤组患者中亦有增高，但差异无统计学意义（P〉0．05）。HCN2的mRNA表达与左心房内径呈正相关（r=0．441，P=0．002）。结论心房肌HCN2、HCN4的mRNA表达水平上调可能是心脏瓣膜病房颤患者心房肌If电流改变的重要分子基础，通过If的改变进一步参与心房的电重构。

Objective The purpose of this study is to evaluate the gene expression of atrial hyperpolarization-activated cyclic nucleotide-gated （HCN） channel informs and regulatory factor and to pursue the molecular mechanism of the hyperpolarization-activated current （ If ） changes in patients with atrial fibrillation （AF）. Methods The left atrial tissue were obtained from 45 patients with valvular heart disease who underwent cardi- ac valve replacement. Twenty-seven patients were in sinus rhythm, 18 patients were in chronic atrial fibrillation. The mRNA level of HCN1, HCN2, HCN4, cAMP were measured by semi-quantitative reverse transcription-poly- merase chain reaction （RT-PCR）. Results Compared to sinus rhythm group, the mRNA level of HCN2 and HCN4 were inereased（P 〈0. 05） in AF group. The mRNA of HCN1 was slightly higher in AF group,but the differences were not statistically significant （ P 〉 0. 05 ）. The mRNA of HCN2 was significantly correlated with the left atial dimension（ r = 0. 441, P = 0. 002 ）. Conclusion The increased mRNA level of atrial HCN2 and HCN4 may be very important molecular mechanism of If changes in patients with atrial fibrillation （AF） , the changes of If were associated with electical remodeling.